We would like to do molecular genetics in eukaryotic systems. We have done some preliminary experiments that suggest that we should be able to do fine-structure mapping in some eukaryotic systems. This project, therefore, is a collaborative effort to refine these preliminary experiments, to devise a general technique for fine- structure mapping in eukaryotes and to apply the methodology to several biological systems of interest. The methodology involves fragmenting the entire eukaryotic genome with restriction enzymes, fractionating the pieces by electrophoresis in gels and assaying for particular portions of the genome by means of RNA/DNA hybridization. We will explore the gene regions for those systems for which one can isolate specific messages; namely the ribosomal genes, the histone region, the hemoglobin genes and the immunoglobulin genes. The ribosome genes should provide us with a system to verify the methodology. The histone region is one worth mapping in preparation for studies of the control mechanisms linking histone and DNA synthesis. The hemoglobin genes will provide a system for the systematic study of the effect of sequence divergence on hybridization. This study will be vital to provide a basis for understanding the results of such experiments with the immunoglobulin genes. We are particularly interested in the immunoglobulin genes since in this case a fine-structure map of the gene organization would be useful in understanding the puzzles presented by our current information about immunoglobulin protein sequences.